Kidney fibrosis is a highly deleterious process and a final manifestation of chronic kidney disease. Alpha-(α)-synuclein (SNCA) is an actin-binding neuronal protein with various functions within the brain; however, its role in other tissues is unknown. Here, we describe the expression of SNCA in renal epithelial cells and demonstrate its decrease in renal tubules of murine and human fibrotic kidneys, as well as its downregulation in renal proximal tubular epithelial cells (RPTECs) after TGF-β1 treatment. shRNA-mediated knockdown of SNCA in RPTECs results in de novo expression of vimentin and α-SMA, while SNCA overexpression represses TGF-β1-induced mesenchymal markers. Conditional gene silencing of SNCA in RPTECs leads to an exacerbated tubulointerstitial fibrosis (TIF) in two unrelated in vivo fibrotic models, which is associated with an increased activation of MAPK-p38 and PI3K-Akt pathways. Our study provides an evidence that disruption of SNCA signaling in RPTECs contributes to the pathogenesis of renal TIF by facilitating partial epithelial-to-mesenchymal transition and extracellular matrix accumulation.

N-Methyl-d-aspartate receptor (NMDAR) is a glutamate-gated ionotropic receptor that intervenes in most of the excitatory synaptic transmission within the central nervous system (CNS). Aside from being broadly distributed in the CNS and having indispensable functions in the brain, NMDAR has predominant roles in many physiological and pathological processes in a wide range of non-neuronal cells and tissues. The present review outlines current knowledge and understanding of the physiological and pathophysiological functions of NMDAR in the kidney, an essential excretory and endocrine organ responsible for the whole-body homeostasis. The review also explores the recent findings regarding signaling pathways involved in NMDAR-mediated responses in the kidney. As established from diverse lines of research reviewed here, basal levels of receptor activation within the kidney are essential for the maintenance of healthy tubular and glomerular function, while a disproportionate activation can lead to a disruption of NMDAR’s downstream signaling pathways and a myriad of pathophysiological consequences.

Obesity is a major global health problem and is associated with a significant risk of renal function decline. Obesity-related nephropathy, as one of the complications of obesity, is characterized by a structural and functional damage of the kidney and represents one of the important contributors to the morbidity and mortality worldwide. Despite increasing data linking hyperlipidemia and lipotoxicity to kidney injury, the apprehension of molecular mechanisms leading to a development of kidney damage is scarce. MicroRNAs (miRNAs) are endogenously produced small noncoding RNA molecules with an important function in post-transcriptional regulation of gene expression. miRNAs have been demonstrated to be important regulators of a vast array of physiological and pathological processes in many organs, kidney being one of them. In this review, we present an overview of miRNAs, focusing on their functional role in the pathogenesis of obesity-associated renal pathologies. We explain novel findings regarding miRNA-mediated signaling in obesity-related nephropathies and highlight advantages and future perspectives of the therapeutic application of miRNAs in renal diseases.